The gastrointestinal (GI) tract in humans refers to the stomach and the intestine and sometimes to all the structures from the mouth to the anus. The upper gastrointestinal tract consists of the esophagus, stomach and duodenum. Some sources also include the mouth cavity and pharynx. The exact demarcation between “upper” and “lower” can vary. Upon gross dissection, the duodenum may appear to be a unified organ, but it is often divided into two parts based upon function, arterial supply, or embryology. The integrated part of GI tract is pancreas and liver named the accessory organs of GI tract.
The lower gastrointestinal tract includes most of the small intestine and all of the large intestine. According to some sources, it also includes the anus. The intestine—or bowel—is divided into the small intestine and the large intestine. The small intestine has three parts: i) duodenum where the digestive juices from pancreas and liver mix together, ii) jejenum which is the midsection of the intestine, connecting duodenum to ileum and iii) ileum which has villi in where all soluble molecules are absorbed into the blood. The large intestine also has three parts: i) caecum where the vermiform appendix is attached to the cecum, ii) colon which consists of the ascending colon, transverse colon, descending colon and sigmoid flexure, and iii) rectum.
The intestine has two main roles: digestion and absorption of nutrients, and maintenance of a barrier against the external environment. It also forms the largest endocrine organ in the body as well as the largest and most complex part of the immune system. In human adults, the intestinal surface area is large, about 100 m2. This large area is continuously exposed to different antigens in the form of food constituents, normal intestinal microflora and pathogens.
The intestinal mucosal surface, also referred to herein as “intestinal tissue”, is lined by a single layer of epithelial cells (IEC) which are continuously and rapidly replaced by replication of undifferentiated cells within the crypt (7×106 cell/min). The epithelial cell layer of the intestinal mucosa is very complex and unique. It secretes digestive enzymes from the apical part to lumen for food digestion. It also secretes different proteins from the second half to the lamina propria (LP). Further, said epithelial cells are receiving signals from both the lumen (and then transmitting the information to the diverse populations of cells in the LP) and the basolateral side. On the basolateral side the intestinal epithelial cells (IECs) receive many signals from various immune cells, nerve cells and stromal cells. Signals on both sides are affected by their respective microenvironments, influencing the functional states, behaviors, and structures of enterocytes resulting in integrity and homeostasis of the gastrointestinal tract.
The protection of the epithelial barrier is guaranteed by junctional complexes composed by tight junctions (TJ) and adherens junctions (AJ) that seal epithelial cells and by production of mucus. The mucus produced also by the specialized epithelial cells, namely goblet cells, provides the first line of defense physical and chemical injury caused by ingested food, microbes and bacterial products. Damage to any part of the GI tract including the goblet cells may lead to an impaired gut barrier, allowing entry of luminal contents into the intestinal wall and initiating chronic inflammation, including inflammation of the GI tract. There is a need for new compositions and methods for preventing and treating gut permeability-related diseases and disorders.